Nitrotyrosine

Nitrotyrosine results from the post-translational modification of the standard amino acid tyrosine. Reactive nitrogen compounds produced in inflammation are typically responsible. Nitrosylation of tyrosine tends to inactivate enzymes.

In March, 2011, there are 13 entries in the PDB containing coordinates for 3-nitrotyrosine (meta-nitro-tyrosine), with the compound ID NIY. These include six sequence-distinct proteins, represented by ribonucleotide reductase 2xof and 2xap, laccase 3div, Human Manganese Superoxide Dismutase 2adp, Human Glutathione Reductase 1k4q, and bovine Cu,Zn superoxide dismutase 1sda. Not surprisingly, the NO2 adduct, being very hydrophilic, is often on the surface of the protein.

 One interesting case is Human Manganese Superoxide Dismutase, for which structures are available for the wild type 2adq, shown at right (restore initial scene ), and the nitrated form, 2adp. In this structure, Mn++ is buried. The Mn++ is caged by four histidine nitrogens, one aspartate oxygen , and one water. Tyrosine 34 is nearby (5.2 &Aring;ngstroms), but not near enough to be interacting with the Mn++ or its cage. Nitrosylation of tyrosine 34 extends it towards the Mn++. The partially negatively charged oxygens in the NO2 are 3.6-3.8 &Aring; from the electron-hungry Mn++. Nitrosylation pushes the tyrosine ring slightly farther from the Mn++, but causes no other significant conformational changes. The authors conclude "Inhibition of catalysis can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate access and binding, and alteration of the hydrogen-bond network that supports proton transfer in catalysis. It is also possible that an electrostatic effect of the nitro group has altered the finely tuned redox potential necessary for efficient catalysis, although the redox potential of nitrated MnSOD has not been measured."